骨髓增生异常综合征大鼠模型的建立及其鉴定

用化学诱变剂二甲基苯蒽(DMBA)诱发大鼠(TR_1)骨髓病变。以35mg/kgDMBA给出生30—45天的大鼠尾静脉注射,分4组,每周分别给药1—4次,其中连续给药2—4次组均可发生明显的骨髓红系和巨核系病态造血,并可进一步发展为白血病,且绝大多数为红白血病。实验结果证明,大鼠2—4次给药后3个月内骨髓象和血象变化与人骨髓增生异常综合征(MDS)相似,其严重程度与DMBA的剂量积累相关,即1次给药组13只大鼠均不发生MDS;2次给药组2/6发生MDS,其中1只发展为白血病;3次给药组9/14发生MDS,其中1只发展为白血病;4次给药组15/16发生MDS,其中8只发展为白血病。3—4次给药组MDS病期为3—4个月,足以满足MDS实验研究。应用v-erbB探针和Southern印迹杂交法,结果显示大鼠MDS及其发展的红白血病与人MDS、红白血病、白血病及恶性肿瘤有相同的c-erbB基因重排和扩增,表明此大鼠MDS模型适合于研究人MDS发病机理与人MDS基因治疗的动物模型。

Establishment and Characterization of a Rat Modei for Myelodysplastic Syndrome Induced by DMBA

The chemical mutagen dimethylbenzanthracene (DMBA) was used to induce rat myelodysplastic syndrome (MDS) by intravenous injection. The dose of DMBA was 35 mg/kg body weight. The rats were divided into 4 groups and injected with DMBA one time weekly and consecutively, 1 - 4 times re-spectively and monitored for 270 days. The dysplastic erythropoiesis and megakaryopoiesis were found in most MDS rats, while trilineage dysplasia were found in a few MDS rats with 4 injection, similar to those of human MDS. Among 2 - 4 times injecting groups, 33.3%, 64. 2%and 93. 7% of rats, re-spectively, developed MDS and then 27. 3% MDS developed into leukemias (all erythroleukemia ex-cept one ALL). Other rats died of infection and bleeding. The disease periods of MDS were 3-4 months. By use of v - erbB probe, the c - erbB rearrangement/amplification in BM celis were found in rat MDS and erythroleukemia (EL), as same as those in human MDS, EL but not in Friend mice EL cells. These results indicated that the model of rat MDS could be used in the study on pathogenesis and gene therapy of human MDS.